A better understanding of the molecular basis of enzymatic breakdown and removal of lipids in lipoprotein complexes is necessary in order to elucidate the pathogenesis of disordered lipid metabolism. For example, a lipase from human post-heparin plasma which is different from lipoprotein lipase from that source and hormone-sensitive lipase from adipose tissue are both obtainable in highly purified forms. Both of these enzymes appear to have phospholipase activity, yet it is difficult to evaluate this activity precisely because of the complicated nature of the interaction of the enzymes with the substrate phospholipid which occurs only in aggregated structures. These enzymes will be evaluated in terms of a "surface dilution" model developed for the study and evaluation of the action of lipolytic enzymes toward substrate in mixed micelle of phospholipid and the nonionic surfactant Triton X-100. This model was developed in studies on phospholipase A2 from Cobra venom (Naja naja naja) which is a pure 11,000 molecular weight enzyme. Additional studies on this latter enzyme are also proposed because of its structural simplicity compared with the human enzymes. All of these studies are aimed at developing a better understanding of the kinetic analysis of the action of phospholipases and other lipolytic enzymes toward substrates in aggregated forms such as lipoprotein complexes, intracellular fat droplets, mixed micelles with bile salts, and membranes. BIBLIOGRAPHIC REFERENCES: M.F. Roberts, R.A. Deems, and E.A. Dennis, Phospholipase A2 (Naja naja naja): Properties and Metal Binding, Feder. Proc. 35, No. 5 (1976) (In press). R.A. Deems, B.R. Dennis, Kinetic Analysis of Phospholipase A2 Activity Toward Mixed Micelles and Its Implications for the Study of Lipolytic Enzymes, J. Biol. Chem. 250, 9013 (1975).